Trial of the MIND Diet for Prevention of Cognitive Decline in Older Persons.

BACKGROUND: Findings from observational studies suggest that dietary patterns may offer protective benefits against cognitive decline, but data from clinical trials are limited. The Mediterranean-DASH Intervention for Neurodegenerative Delay, known as the MIND diet, is a hybrid of the Mediterranean diet and the DASH (Dietary Approaches to Stop Hypertension) diet, with modifications to include foods that have been putatively associated with a decreased risk of dementia. METHODS: We performed a two-site, randomized, controlled trial involving older adults without cognitive impairment but with a family history of dementia, a body-mass index (the weight in kilograms divided by the square of the height in meters) greater than 25, and a suboptimal diet, as determined by means of a 14-item questionnaire, to test the cognitive effects of the MIND diet with mild caloric restriction as compared with a control diet with mild caloric restriction. We assigned the participants in a 1:1 ratio to follow the intervention or the control diet for 3 years. All the participants received counseling regarding adherence to their assigned diet plus support to promote weight loss. The primary end point was the change from baseline in a global cognition score and four cognitive domain scores, all of which were derived from a 12-test battery. The raw scores from each test were converted to z scores, which were averaged across all tests to create the global cognition score and across component tests to create the four domain scores; higher scores indicate better cognitive performance. The secondary outcome was the change from baseline in magnetic resonance imaging (MRI)-derived measures of brain characteristics in a nonrandom sample of participants. RESULTS: A total of 1929 persons underwent screening, and 604 were enrolled; 301 were assigned to the MIND-diet group and 303 to the control-diet group. The trial was completed by 93.4% of the participants. From baseline to year 3, improvements in global cognition scores were observed in both groups, with increases of 0.205 standardized units in the MIND-diet group and 0.170 standardized units in the control-diet group (mean difference, 0.035 standardized units; 95% confidence interval, -0.022 to 0.092; P = 0.23). Changes in white-matter hyperintensities, hippocampal volumes, and total gray- and white-matter volumes on MRI were similar in the two groups. CONCLUSIONS: Among cognitively unimpaired participants with a family history of dementia, changes in cognition and brain MRI outcomes from baseline to year 3 did not differ significantly between those who followed the MIND diet and those who followed the control diet with mild caloric restriction. (Funded by the National Institute on Aging; ClinicalTrials.gov number, NCT02817074.).

School racial composition, effect modification by caring teacher/staff presence, and mid/late-life depressive symptoms: findings from the Study of Healthy Aging among African Americans.

For Black students in the United States, attending schools with a higher proportion of White students is associated with worse mental and physical health outcomes in adolescence/early adulthood. No prior studies evaluate K-12 school racial composition and later-life mental health. In a cohort of Black adults ages 50+ in Northern California who retrospectively self-reported school racial composition for grades 1, 6, 9, and 12, we assessed the association between attending a school with mostly Black students vs. not and mid/late-life depressive symptoms (8-item PROMIS depression score, standardized to US adult population) using age-, sex/gender-, southern US birth-, and parental education-adjusted generalized estimating equations, and assessed effect modification by caring teacher/staff presence. Later-life depressive symptoms were lower among those who attended schools with mostly Black students in grades 1 and 6 (b=-0.12, 95% CI: -0.23, 0.00 and b=-0.11, 95% CI: -0.22, 0.00, respectively). In grade 6, this difference was larger for students without an adult at school who cared about them (b=-0.29, 95% CI: -0.51, -0.07 vs. b=-0.04, 95% CI: -0.17, 0.09). Among Black Americans, attending early school with mostly Black students may have later life mental health benefits; this protective association appears more important for students without caring teachers/staff.

Childhood and Adulthood Trauma Associate With Cognitive Aging Among Black and White Older Adults.

Sociocontextual factors powerfully shape risk for age-related cognitive impairment, including excess risk burdening medically underserved populations. Lifecourse adversity associates with cognitive aging, but harms are likely mitigable. Understanding population-salient relationships and sensitive periods for exposure is crucial for targeting clinical interventions. OBJECTIVE: The authors examined childhood and adulthood traumatic events in relation to cognition among Black and White older adults in the Health and Retirement Study (HRS). PARTICIPANTS: Participants (N = 13,952) aged 55+ had complete lifetime trauma and cognitive testing data at the 2006/08, 2010/12, and/or 2014/16 waves. MEASURES: Trauma indices comprised childhood and adulthood event counts. Outcomes included baseline performance and trajectories on the Telephone Interview for Cognitive Status. DESIGN: Main and nonlinear trauma effects were modeled via linear regression, and overall contributions assessed with omnibus likelihood ratio tests. RESULTS: Black participants (N = 2,345) reported marginally lower adulthood trauma exposure than White participants (N = 11,607) with no other exposure differentials observed. In White participants only, greater childhood trauma exposure predicted worse baseline cognition but slower change over time. Across race, adulthood trauma robustly associated with baseline cognition. Relationships were frequently nonlinear: low but nonzero trauma predicted highest cognitive scores, with much poorer cognition observed as trauma exposure increased. Relationships between adulthood trauma and trajectory were limited to the White sample. CONCLUSION: Traumatic experiences, particularly in adulthood, may impact late-life cognitive health if not addressed. Findings highlight foci for clinical researchers and providers: adverse life events as a source of cognitive risk, and identification of community-specific resources that buffer behavioral, physical, and mental health sequelae of previous and incident trauma.

Age-related and amyloid-beta-independent tau deposition and its downstream effects.

Amyloid-ß (Aß) is hypothesized to facilitate the spread of tau pathology beyond the medial temporal lobe. However, there is evidence that, independently of Aß, age-related tau pathology might be present outside of the medial temporal lobe. We therefore aimed to study age-related Aß-independent tau deposition outside the medial temporal lobe in two large cohorts and to investigate potential downstream effects of this on cognition and structural measures. We included 545 cognitively unimpaired adults (40-92 years) from the BioFINDER-2 study (in vivo) and 639 (64-108 years) from the Rush Alzheimer's Disease Center cohorts (ex vivo). 18F-RO948- and 18F-flutemetamol-PET standardized uptake value ratios were calculated for regional tau and global/regional Aß in vivo. Immunohistochemistry was used to estimate Aß load and tangle density ex vivo. In vivo medial temporal lobe volumes (subiculum, cornu ammonis 1) and cortical thickness (entorhinal cortex, Brodmann area 35) were obtained using Automated Segmentation for Hippocampal Subfields packages. Thickness of early and late neocortical Alzheimer's disease regions was determined using FreeSurfer. Global cognition and episodic memory were estimated to quantify cognitive functioning. In vivo age-related tau deposition was observed in the medial temporal lobe and in frontal and parietal cortical regions, which was statistically significant when adjusting for Aß. This was also observed in individuals with low Aß load. Tau deposition was negatively associated with cortical volumes and thickness in temporal and parietal regions independently of Aß. The associations between age and cortical volume or thickness were partially mediated via tau in regions with early Alzheimer's disease pathology, i.e. early tau and/or Aß pathology (subiculum/Brodmann area 35/precuneus/posterior cingulate). Finally, the associations between age and cognition were partially mediated via tau in Brodmann area 35, even when including Aß-PET as covariate. Results were validated in the ex vivo cohort showing age-related and Aß-independent increases in tau aggregates in and outside the medial temporal lobe. Ex vivo age-cognition associations were mediated by medial and inferior temporal tau tangle density, while correcting for Aß density. Taken together, our study provides support for primary age-related tauopathy even outside the medial temporal lobe in vivo and ex vivo, with downstream effects on structure and cognition. These results have implications for our understanding of the spreading of tau outside the medial temporal lobe, also in the context of Alzheimer's disease. Moreover, this study suggests the potential utility of tau-targeting treatments in primary age-related tauopathy, likely already in preclinical stages in individuals with low Aß pathology.

Correlates of missed or late versus timely diagnosis of dementia in healthcare settings.

INTRODUCTION: There is limited evidence about factors related to the timeliness of dementia diagnosis in healthcare settings. METHODS: In five prospective cohorts at Rush Alzheimer's Disease Center, we identified participants with incident dementia based on annual assessments and examined the timing of healthcare diagnoses in Medicare claims. We assessed sociodemographic, health, and psychosocial correlates of timely diagnosis. RESULTS: Of 710 participants, 385 (or 54%) received a timely claims diagnosis within 3 years prior to or 1 year following dementia onset. In logistic regressions accounting for demographics, we found Black participants (odds ratio [OR] = 2.15, 95% confidence interval [CI]: 1.21 to 3.82) and those with better cognition at dementia onset (OR = 1.48, 95% CI: 1.10 to 1.98) were at higher odds of experiencing a diagnostic delay, whereas participants with higher income (OR = 0.89, 95% CI: 0.81 to 0.97) and more comorbidities (OR = 0.94, 95% CI: 0.89 to 0.98) had lower odds. DISCUSSION: We identified characteristics of individuals who may miss the optimal window for dementia treatment and support. HIGHLIGHTS: We compared the timing of healthcare diagnosis relative to the timing of incident dementia based on rigorous annual evaluation. Older Black adults with lower income, higher cognitive function, and fewer comorbidities were less likely to be diagnosed in a timely manner by the healthcare system.

Sex-specific genetic architecture of late-life memory performance.

BACKGROUND: Women demonstrate a memory advantage when cognitively healthy yet lose this advantage to men in Alzheimer's disease. However, the genetic underpinnings of this sex difference in memory performance remain unclear. METHODS: We conducted the largest sex-aware genetic study on late-life memory to date (Nmales  = 11,942; Nfemales  = 15,641). Leveraging harmonized memory composite scores from four cohorts of cognitive aging and AD, we performed sex-stratified and sex-interaction genome-wide association studies in 24,216 non-Hispanic White and 3367 non-Hispanic Black participants. RESULTS: We identified three sex-specific loci (rs67099044-CBLN2, rs719070-SCHIP1/IQCJ-SCHIP), including an X-chromosome locus (rs5935633-EGL6/TCEANC/OFD1), that associated with memory. Additionally, we identified heparan sulfate signaling as a sex-specific pathway and found sex-specific genetic correlations between memory and cardiovascular, immune, and education traits. DISCUSSION: This study showed memory is highly and comparably heritable across sexes, as well as highlighted novel sex-specific genes, pathways, and genetic correlations that related to late-life memory. HIGHLIGHTS: Demonstrated the heritable component of late-life memory is similar across sexes. Identified two genetic loci with a sex-interaction with baseline memory. Identified an X-chromosome locus associated with memory decline in females. Highlighted sex-specific candidate genes and pathways associated with memory. Revealed sex-specific shared genetic architecture between memory and complex traits.

Longitudinal change in memory performance as a strong endophenotype for Alzheimer's disease.

INTRODUCTION: Although large-scale genome-wide association studies (GWAS) have been conducted on AD, few have been conducted on continuous measures of memory performance and memory decline. METHODS: We conducted a cross-ancestry GWAS on memory performance (in 27,633 participants) and memory decline (in 22,365 participants; 129,201 observations) by leveraging harmonized cognitive data from four aging cohorts. RESULTS: We found high heritability for two ancestry backgrounds. Further, we found a novel ancestry locus for memory decline on chromosome 4 (rs6848524) and three loci in the non-Hispanic Black ancestry group for memory performance on chromosomes 2 (rs111471504), 7 (rs4142249), and 15 (rs74381744). In our gene-level analysis, we found novel genes for memory decline on chromosomes 1 (SLC25A44), 11 (BSX), and 15 (DPP8). Memory performance and memory decline shared genetic architecture with AD-related traits, neuropsychiatric traits, and autoimmune traits. DISCUSSION: We discovered several novel loci, genes, and genetic correlations associated with late-life memory performance and decline. HIGHLIGHTS: Late-life memory has high heritability that is similar across ancestries. We discovered four novel variants associated with late-life memory. We identified four novel genes associated with late-life memory. Late-life memory shares genetic architecture with psychiatric/autoimmune traits.

Brain copper may protect from cognitive decline and Alzheimer's disease pathology: a community-based study.

Copper is an essential micronutrient for brain health and dyshomeostasis of copper could have a pathophysiological role in Alzheimer's disease (AD), however, there are limited data from community-based samples. In this study, we investigate the association of brain copper (assessed using ICP-MS in four regions -inferior temporal, mid-frontal, anterior cingulate, and cerebellum) and dietary copper with cognitive decline and AD pathology burden (a quantitative summary of neurofibrillary tangles, diffuse and neuritic plaques in multiple brain regions) at autopsy examination among deceased participants (N = 657; age of death: 90.2(±6.2)years, 70% women, 25% APOE-ɛ4 carriers) in the Rush Memory and Aging Project. During annual visits, these participants completed cognitive assessments using a 19-test battery and dietary assessments (using a food frequency questionnaire). Regression, linear mixed-effects, and logistic models adjusted for age at death, sex, education, and APOE-ε4 status were used. Higher composite brain copper levels were associated with slower cognitive decline (ß(SE) = 0.028(0.01), p = 0.001) and less global AD pathology (ß(SE) = -0.069(0.02), p = 0.0004). Participants in the middle and highest tertile of dietary copper had slower cognitive decline (T2vs.T1: ß = 0.038, p = 0.0008; T3vs.T1: ß = 0.028, p = 0.01) than those in the lowest tertile. Dietary copper intake was not associated with brain copper levels or AD pathology. Associations of higher brain copper levels with slower cognitive decline and with less AD pathology support a role for copper dyshomeostasis in AD pathogenesis and suggest that lower brain copper may exacerbate or indicate disease severity. Dietary and brain copper are unrelated but dietary copper is associated with slower cognitive decline via an unknown mechanism.

Perceptions of Caring Recruitment Among Older Adults: African Americans and Non-Latinx Whites.

BACKGROUND: African Americans (AAs) are underrepresented in health-related research studies. Few studies have investigated how behaviors of study recruiters affect recruitment of older AAs versus non-Latinx Whites (NLWs). OBJECTIVES: The aim of this study was to explore whether caring behaviors influence AA and NLW older adults' decision to participate in hypothetical, high-commitment, health-related research studies and differences in participants' enrollment decisions by race. METHODS: Using a descriptive, cross-sectional study design, guided by Kristen Swanson's middle-range theory of caring, a research-savvy sample of 60 AA and 60 NLW adults (age > 65 years) were randomly assigned one of two written vignettes. The concept of caring behaviors was manipulated and illustrated in a hypothetical recruitment scenario. A participant feedback survey was used to assess (a) participants' perceptions of caring and uncaring behaviors exhibited by the fictitious research recruiter, (b) differences in their willingness to participate based on vignette type, and (c) participants' judgment of the research recruiter as being caring or uncaring. A chi-square test assessed the association among categorical variables (caring behavior and participants' race). RESULTS: Participants who received the vignette with the high caring recruiter were more than twice as likely to agree to participate in the study than those who received the vignette with the low caring recruiter. AA and NLW participants did not differ in their likelihood to agree to participate. Participants who received the caring vignette and judged the recruiter as caring were 5 times as likely to agree to participate in the high-commitment study than those who received the uncaring vignette ( p < .001). Associations did not vary by race. DISCUSSION: This experimental study of equally recruited older adults from an existing longitudinal study revealed that caring behaviors in recruitment strategies are associated with an increased likelihood of participation in high-commitment research with older adults. The research-savvy AA participants were just as likely to participate in the hypothetical high-commitment research as their NLW peers when the fictional research recruiter was perceived as having caring behaviors. When targeting specific populations, it is essential to employ nuanced recruitment approaches where the study recruiters are attuned to caring behaviors.

Overcoming Pandemic-Related Challenges in Recruitment and Screening: Strategies and Representation of Older Women With Cardiovascular Disease for a Multidomain Lifestyle Trial to Prevent Cognitive Decline.

BACKGROUND: Recruiting participants with cardiovascular disease into research during the COVID-19 pandemic was challenging, particularly those at risk of health disparities. OBJECTIVE: During the pandemic, 12 cohorts of older women with cardiovascular disease were recruited from cardiology clinics into a lifestyle intervention trial to prevent cognitive decline. Objectives were to (a) describe the results of modified recruitment/screening strategies to overcome pandemic-related challenges and (b) evaluate differences in age, race, and ethnicity between patients recruited/randomized, recruited/not randomized (entered recruitment but not randomized because of being ineligible or not interested), and not recruited (clinic patients who met preliminary criteria but did not enter recruitment). METHODS: This was a cross-sectional descriptive analysis. In-person study strategies proposed before the COVID-19 pandemic were modified before study onset (September 2020). Women 65 years or older with cardiovascular disease were recruited from cardiology clinics by clinicians, posted flyers, and letters mailed to patients randomly selected from electronic health record data extractions. Patients were classified as recruited/randomized, recruited/not randomized, and not recruited. RESULTS: Of 5719 patients potentially eligible, 1689 patients entered recruitment via referral (49.1%), posted flyers (0.5%), or mailed letters (50.3%), and 253 patients were successfully recruited/randomized. Recruited/randomized participants were, on average, 72.4 years old (range, 65-90 years old), non-Hispanic White (54.2%), non-Hispanic Black (38.3%), Hispanic/Latinx (1.6%), and other/not reported (5.1%). The recruited/randomized group was significantly younger with fewer patients of Hispanic/Latinx ethnicity compared with those not recruited. CONCLUSIONS: During the pandemic, all recruitment/screening goals were met using modified strategies. Differences in sociodemographic representation indicate a need for tailored strategies.

Vitamin D intake and cognitive decline in Blacks and Whites: The role of diet and supplements.

INTRODUCTION: To determine the role of vitamin D intake on cognitive decline among Blacks and Whites. METHODS: Using data from the population-based Chicago Health and Aging Project, we studied 2061 Blacks and 1329 Whites with dietary vitamin D data and cognitive testing over 12 years of follow-up. Multivariable linear mixed-effects models were used to determine the association of vitamin D intake with cognitive decline. RESULTS: Vitamin D intake, particularly dietary vitamin D, was associated with a slower rate of decline in cognitive function among Blacks. In Blacks, comparing individuals in the lowest tertile of dietary intake, those in the highest tertile had a slower cognitive decline of 0.017 units/year (95% confidence interval 0.006, 0.027), independently of supplementation use. In Whites, vitamin D intake was not associated with cognitive decline. DISCUSSION: Dietary vitamin D may help to slow the decline in cognitive abilities among Blacks as they age.

Evaluating interpersonal discrimination and depressive symptoms as partial mediators of the effects of education on cognition: Evidence from the Study of Healthy Aging in African Americans (STAR).

INTRODUCTION: Education is correlated with positive health outcomes, but associations are sometimes weaker among African Americans. The extent to which exposure to discrimination and depressive symptoms attenuates the education-cognition link has not been investigated. METHODS: Study of Healthy Aging in African Americans (STAR) participants (n = 764; average age 69 years) completed the Spanish and English Neuropsychological Assessment Scales. We assessed everyday and major lifetime discrimination and depressive symptoms as mediators of education effects on cognition using G-estimation with measurement error corrections. RESULTS: Education was correlated with greater major lifetime and everyday discrimination but lower depressive symptoms. Accounting for discrimination and depressive symptoms slightly reduced the estimated effect of education on cognition. The estimated total effect of graduate education (vs 

The impact of attending historically Black colleges and universities on cognitive decline in Black adults: A longitudinal analysis in the KHANDLE and STAR cohorts.

INTRODUCTION: Black students attending predominantly White institutions (PWIs) versus historically Black colleges and universities (HBCUs) report more harmful discrimination and develop worse mental health outcomes, potentially offsetting the established benefits of college for lowering dementia incidence. METHODS: Black participants in two cohorts (the Kaiser Healthy Aging and Diverse Life Experiences [KHANDLE] and the Study of Healthy Aging in African Americans [STAR]) who had attended college (N = 716) self-reported the college name (classified as HBCU vs. PWI) and completed three waves of executive function (EF) and verbal episodic memory (VEM) assessments. HBCU effects on cognitive level and decline were estimated using adjusted linear mixed-effects models. RESULTS: HBCU (vs. PWI) attendees averaged better EF (ß = 0.05 [-0.22, 0.32]) and VEM (ß = 0.21 [-0.06, 0.46]) at age 70 though neither association was statistically significant. HBCU attendance was associated with slightly faster VEM decline (ß = -0.03 [-0.05, 0.00]). DISCUSSION: Harmonized analyses with larger studies are needed to estimate important effects of HBCU attendance. HIGHLIGHTS: Higher education is robustly linked to lower dementia risk, yet Black-White inequities persist among college-educated adults. Black students attending predominantly White institutions (PWIs) versus historically Black colleges and universities (HBCUs) report more harmful discrimination and develop worse mental health outcomes, which may offset the established benefits of college for lowering dementia incidence. HBCU (vs. non-HBCU) attendees averaged better executive function and verbal episodic memory (VEM) at average age 70, though confidence intervals were wide and associations were not statistically significant, and averaged slightly faster decline in VEM. Harmonized analyses using larger nationally representative studies are likely needed to avoid underestimating the health effects of HBCU attendance.

Pragmatic approaches to handling practice effects in longitudinal cognitive aging research.

INTRODUCTION: The challenge of accounting for practice effects (PEs) when modeling cognitive change was amplified by the COVID-19 pandemic, which introduced period and mode effects that may bias the estimation of cognitive trajectory. METHODS: In three Kaiser Permanente Northern California prospective cohorts, we compared predicted cognitive trajectories and the association of grip strength with cognitive decline using three approaches: (1) no acknowledgment of PE, (2) inclusion of a wave indicator, and (3) constraining PE based on a preliminary model (APM) fit using a subset of the data. RESULTS: APM-based correction for PEs based on balanced, pre-pandemic data, and with current age as the timescale produced the smallest discrepancy between within-person and between-person estimated age effects. Estimated associations between grip strength and cognitive decline were not sensitive to the approach used. DISCUSSION: Constraining PEs based on a preliminary model is a flexible, pragmatic approach allowing for meaningful interpretation of cognitive change. HIGHLIGHTS: The magnitude of practice effects (PEs) varied widely by study. When PEs were present, the three PE approaches resulted in divergent estimated age-related cognitive trajectories. Estimated age-related cognitive trajectories were sometimes implausible in models that did not account for PEs. The associations between grip strength and cognitive decline did not differ by the PE approach used. Constraining PEs based on estimates from a preliminary model allows for a meaningful interpretation of cognitive change.

The association of perceived discrimination with dementia risk in Black older adults.

INTRODUCTION: Non-Hispanic Black, compared to non-Hispanic White, older adults are at increased risk for dementia. This may be due partly to greater exposure to psychosocial stressors, such as discrimination; however, few studies have examined this association. METHODS: We examined the association of perceived discrimination (e.g., everyday, lifetime, and discrimination burden) with dementia risk in 1583 Black adults co-enrolled in the Atherosclerosis Risk in Communities (ARIC) Study and the Jackson Heart Study (JHS). Perceived discrimination (defined continuously and using tertiles) was assessed at JHS Exam 1 (2000-2004; mean age ± SD:66.2 ± 5.5) and related to dementia risk through ARIC visit 6 (2017) using covariate-adjusted Cox proportional hazards models. RESULTS: Associations of perceived everyday, lifetime, and burden of discrimination with dementia risk were not supported in age-adjusted models or demographic- and cardiovascular health-adjusted models. Results were similar across sex, income, and education. DISCUSSION: In this sample, associations between perceived discrimination and dementia risk were not supported. HIGHLIGHTS: In Black older adults perceived discrimination not associated with dementia risk. Younger age and greater education linked to greater perceived discrimination. Older age and less education among factors associated with dementia risk. Factors increasing exposure to discrimination (education) are also neuroprotective.

Sex differences in associations between APOE ε2 and longitudinal cognitive decline.

INTRODUCTION: We examined whether sex modifies the association between APOE ε2 and cognitive decline in two independent samples. METHODS: We used observational data from cognitively unimpaired non-Hispanic White (NHW) and non-Hispanic Black (NHB) adults. Linear mixed models examined interactive associations of APOE genotype (ε2 or ε4 carrier vs. ε3/ε3) and sex on cognitive decline in NHW and NHB participants separately. RESULTS: In both Sample 1 (N = 9766) and Sample 2 (N = 915), sex modified the association between APOE ε2 and cognitive decline in NHW participants. Specifically, relative to APOE ε3/ε3, APOE ε2 protected against cognitive decline in men but not women. Among APOE ε2 carriers, men had slower decline than women. Among APOE ε3/ε3 carriers, cognitive trajectories did not differ between sexes. There were no sex-specific associations of APOE ε2 with cognition in NHB participants (N = 2010). DISCUSSION: In NHW adults, APOE ε2 may protect men but not women against cognitive decline. HIGHLIGHTS: We studied sex-specific apolipoprotein E (APOE) ε2 effects on cognitive decline. In non-Hispanic White (NHW) adults, APOE ε2 selectively protects men against decline. Among men, APOE ε2 was more protective than APOE ε3/ε3. In women, APOE ε2 was no more protective than APOE ε3/ε3. Among APOE ε2 carriers, men had slower decline than women. There were no sex-specific APOE ε2 effects in non-Hispanic Black (NHB) adults.

Complex Profiles of Cerebrovascular Disease Pathologies in the Aging Brain and Their Relationship With Cognitive Decline.

BACKGROUND AND PURPOSE: Cerebrovascular disease (CVD) pathologies including vessel disease (atherosclerosis, arteriolosclerosis, and cerebral amyloid angiopathy) and tissue injury (macroinfarcts and microinfarcts) each contribute to Alzheimer and other forms of dementia. CVD is often a complex mix of neuropathologies, with little known about the frequencies of differing combinations or their associations with cognition. METHODS: We investigated 32 possible CVD combinations (3 types of vessel disease and 2 types of tissue injury) using autopsy data from 1474 decedents (≈88 years at death; 65% female) of Rush Alzheimer's Disease Center studies. We determined frequencies of all 32 CVD combinations and their relationships with global and domain-specific cognitive decline using mixed-effect models adjusted for demographics, neuropathologies, time before death, and interactions of these variables with time. RESULTS: Of the 1184 decedents with CVD neuropathology (80% of the total sample), 37% had a single CVD (67-148 decedents/group) while 63% had mixed CVD profiles (11-54 decedents/group). When considered as 2 distinct groups, the mixed CVD profile group (but not the single CVD profile group) showed a faster cognitive decline across all domains assessed compared with decedents without CVD neuropathology. Most mixed CVD profiles, especially those involving both atherosclerosis and arteriolosclerosis, showed faster cognitive decline than any single CVD profile considered alone; specific mixed CVD profiles differentially associated with individual cognitive domains. CONCLUSIONS: Mixed CVD, more common than single CVD, is associated with cognitive decline, and distinct mixed CVD profiles show domain-specific associations with cognitive decline. CVD is not monolithic but consists of heterogenous person-specific combinations with distinct contributions to cognitive decline.

Cognitive decline and hippocampal functional connectivity within older Black adults.

While there has been a proliferation of neuroimaging studies on cognitive decline in older non-Hispanic White adults, there is a dearth of knowledge regarding neuroimaging correlates of cognitive decline in Black adults. Resting-state functional neuroimaging approaches may be particularly sensitive to early cognitive decline, but there are no studies that we know of that apply this approach to examining associations of brain function to cognition in older Black adults. We investigated the association of cognitive decline with whole-brain voxel-wise functional connectivity to the hippocampus, a key brain region functionally implicated in early Alzheimer's dementia, in 132 older Black adults without dementia participating in the Minority Aging Research Study and Rush Memory and Aging Project, two longitudinal studies of aging that include harmonized annual cognitive assessments and magnetic resonance imaging brain imaging. In models adjusted for demographic factors (age, education, sex), global cognitive decline was associated with functional connectivity of the hippocampus to three clusters in the right and left frontal regions of the dorsolateral prefrontal cortex. In domain-specific analyses, decline in semantic memory was associated with functional connectivity of the hippocampus to bilateral clusters in the precentral gyrus, and decline in perceptual speed was inversely associated with connectivity of the hippocampus to the bilateral intracalcarine cortex and the right fusiform gyrus. These findings elucidate neurobiological mechanisms underlying cognitive decline in older Black adults and may point to specific targets of intervention for Alzheimer's disease.

The Relationship of John Henryism With Cognitive Function and Decline in Older Black Adults.

OBJECTIVE: This study aimed to investigate the relationship between John Henryism, a psychological trait typified by high-effort active coping that has been associated with adverse health outcomes among Blacks, and cognitive decline. METHODS: In a cohort of community-dwelling older Black adults ( N = 611), we investigated the relationship between John Henryism and cognitive decline. John Henryism was measured using the John Henryism Active Coping Scale (JHACS), a nine-item validated measure of self-reported high-effort coping (mean [standard deviation] = 16.9 [4.8]; range, 4-27). We implemented a three-step modeling process using mixed-effects models to assess the relationship between the JHACS and global cognitive function as well as five cognitive domains. We adjusted for demographics and for factors known to be associated with cognitive function and decline including vascular risk factors, discrimination, and income. RESULTS: The trait of high-effort active coping was associated with lower-average cognitive function ( ß = -0.07, 95% confidence interval = -0.10 to -0.03), but not with decline. The results remained after further adjustment for experiences of discrimination, income, and vascular risk factors. In domain-specific analyses, we found that the JHACS was associated with baseline levels of working memory, semantic memory, and visuospatial ability, but not decline. CONCLUSIONS: These results highlight the importance of using culturally specific measures in considering the heterogeneity of cognitive health outcomes in minoritized populations. Understanding how stress responses relate to late-life cognition among older Black adults could help promote aspects of behavioral resilience along with healthful coping responses.

Relationship of Blood Pressure and White Matter Hyperintensity Burden With Level of and Change in Cognition in Older Black Adults.

OBJECTIVE: Elevations in blood pressure (BP) and associated white matter hyperintensities (WMHs) are chronic comorbid conditions among older Black adults. We investigated whether WMHs modify the association between late-life BP and cognition within older Black adults. METHODS: A total of 167 Black adults (age, ~75 years; without dementia at baseline) participating in neuroimaging studies at the Rush Alzheimer's Disease Center were evaluated for BP markers of cardiovascular health, including systolic BP, diastolic BP, pulse pressure, mean arterial pressure (MAP), and hypertension, and were assessed for global and domain-specific cognition at baseline and annually for up to 8 years. WMHs adjusted for intracranial volume were quantified at baseline. RESULTS: Models adjusted for relevant confounders and the interaction of these variables with time revealed differential associations between BP markers and baseline cognition; however, only elevated diastolic BP predicted faster cognitive, that is, episodic memory, decline (estimate = -0.002, standard error = 0.0009, p = .002). Although WMH burden did not modify the association between diastolic BP and episodic memory decline, it did interact with diastolic BP to lower episodic memory at baseline (estimate = -0.051, standard error = 0.012, p = .0001); that is, greater WMHs combined with higher diastolic BP resulted in the lowest baseline episodic memory scores. A similar profile was noted for WMHs, MAP, and baseline episodic memory. Hypertension was neither associated with cognition nor modified by WMH burden after multiple comparisons correction. CONCLUSION: Late-life diastolic BP was associated with faster rates of episodic memory decline in older Black adults; together with higher WMH burden, it (and MAP) lowered the point at which individuals begin their course of decline toward pathological aging.